Attenuating apoptosis in Chinese hamster ovary cells for improved biopharmaceutical production

Chinese hamster ovary (CHO) cells are the predominant host cell line for the production of biopharmaceuticals, a growing industry currently worth more than $188 billion USD in global sales. CHO cells undergo programmed cell death (apoptosis) following different stresses encountered in cell culture,...

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Published inBiotechnology and bioengineering Vol. 117; no. 4; pp. 1187 - 1203
Main Authors Henry, Matthew N., MacDonald, Michael A., Orellana, Camila A., Gray, Peter P., Gillard, Marianne, Baker, Kym, Nielsen, Lars K., Marcellin, Esteban, Mahler, Stephen, Martínez, Verónica S.
Format Journal Article
LanguageEnglish
Published United States Wiley Subscription Services, Inc 01.04.2020
Subjects
Animals
Apoptosis
Biological Products - metabolism
biopharmaceutical production
Biopharmaceuticals
Biotechnology
Cell culture
Cell Culture Techniques
Cell death
Cell Engineering
CHO cell line engineering
CHO Cells
Cricetinae
Cricetulus
Genetic engineering
programmed cell death
Substrates
Toxicity
CHO cell line engineering
apoptosis
programmed cell death
biopharmaceutical production
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Abstract Chinese hamster ovary (CHO) cells are the predominant host cell line for the production of biopharmaceuticals, a growing industry currently worth more than $188 billion USD in global sales. CHO cells undergo programmed cell death (apoptosis) following different stresses encountered in cell culture, such as substrate limitation, accumulation of toxic by‐products, and mechanical shear, hindering production. Genetic engineering strategies to reduce apoptosis in CHO cells have been investigated with mixed results. In this review, a contemporary understanding of the real complexity of apoptotic mechanisms and signaling pathways is described; followed by an overview of antiapoptotic cell line engineering strategies tested so far in CHO cells. Chinese Hamster Ovary cell death, or apoptosis, poses a significant bioprocessing challenge, in particular for high cell density culture. Here, the main known mechanisms of apoptosis, triggered by external and internal signals, are explained. A critical summary of previous cell line engineering strategies used to inhibit apoptosis follows. This review, combined with CRISPR‐Cas9 based gene editing technologies, will expedite rational genetic engineering of biopharmaceutical production cell lines in the near future.
AbstractList Chinese hamster ovary (CHO) cells are the predominant host cell line for the production of biopharmaceuticals, a growing industry currently worth more than $188 billion USD in global sales. CHO cells undergo programmed cell death (apoptosis) following different stresses encountered in cell culture, such as substrate limitation, accumulation of toxic by‐products, and mechanical shear, hindering production. Genetic engineering strategies to reduce apoptosis in CHO cells have been investigated with mixed results. In this review, a contemporary understanding of the real complexity of apoptotic mechanisms and signaling pathways is described; followed by an overview of antiapoptotic cell line engineering strategies tested so far in CHO cells.
Chinese hamster ovary (CHO) cells are the predominant host cell line for the production of biopharmaceuticals, a growing industry currently worth more than $188 billion USD in global sales. CHO cells undergo programmed cell death (apoptosis) following different stresses encountered in cell culture, such as substrate limitation, accumulation of toxic by‐products, and mechanical shear, hindering production. Genetic engineering strategies to reduce apoptosis in CHO cells have been investigated with mixed results. In this review, a contemporary understanding of the real complexity of apoptotic mechanisms and signaling pathways is described; followed by an overview of antiapoptotic cell line engineering strategies tested so far in CHO cells. Chinese Hamster Ovary cell death, or apoptosis, poses a significant bioprocessing challenge, in particular for high cell density culture. Here, the main known mechanisms of apoptosis, triggered by external and internal signals, are explained. A critical summary of previous cell line engineering strategies used to inhibit apoptosis follows. This review, combined with CRISPR‐Cas9 based gene editing technologies, will expedite rational genetic engineering of biopharmaceutical production cell lines in the near future.
Author Orellana, Camila A.
Gray, Peter P.
MacDonald, Michael A.
Baker, Kym
Mahler, Stephen
Martínez, Verónica S.
Nielsen, Lars K.
Henry, Matthew N.
Gillard, Marianne
Marcellin, Esteban
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  orcidid: 0000-0003-2729-5278
  surname: Martínez
  fullname: Martínez, Verónica S.
  email: v.salazar@uq.edu.au
  organization: Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland
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Issue 4
Keywords CHO cell line engineering
apoptosis
programmed cell death
biopharmaceutical production
Language English
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Notes Matthew N. Henry and Michael A. MacDonald contributed equally to this work.
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PublicationTitle Biotechnology and bioengineering
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Snippet Chinese hamster ovary (CHO) cells are the predominant host cell line for the production of biopharmaceuticals, a growing industry currently worth more than...
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SubjectTerms Animals
Apoptosis
Biological Products - metabolism
biopharmaceutical production
Biopharmaceuticals
Biotechnology
Cell culture
Cell Culture Techniques
Cell death
Cell Engineering
CHO cell line engineering
CHO Cells
Cricetinae
Cricetulus
Genetic engineering
programmed cell death
Substrates
Toxicity
Title Attenuating apoptosis in Chinese hamster ovary cells for improved biopharmaceutical production
URI https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fbit.27269
https://www.ncbi.nlm.nih.gov/pubmed/31930480
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